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. 2013 Jun;139(3):667-76.
doi: 10.1007/s10549-013-2581-3. Epub 2013 Jun 12.

The presence of programmed death 1 (PD-1)-positive tumor-infiltrating lymphocytes is associated with poor prognosis in human breast cancer

S Muenst  1 , S D Soysal, F Gao, E C Obermann, D Oertli, W E Gillanders
Affiliations

The presence of programmed death 1 (PD-1)-positive tumor-infiltrating lymphocytes is associated with poor prognosis in human breast cancer

S Muenst et al. Breast Cancer Res Treat. 2013 Jun.

Abstract

Programmed death 1 (PD-1) is a co-inhibitory receptor in the CD28/CTL-4 family, and functions as a negative regulator of the immune system. Tumor-infiltrating lymphocytes (TIL) in many epithelial cancers express PD-1, suggesting that antitumor immunity may be modulated by the PD-1/PD-L1 signaling pathway, and promising results from two recent clinical trials with monoclonal antibodies targeting PD-1 or PD-L1 confirm the clinical relevance of this pathway in human cancer. To explore the role of PD-1(+) TIL in human breast cancer, we performed immunohistochemistry studies on a tissue microarray encompassing 660 breast cancer cases with detailed clinical annotation and outcomes data. PD-1(+) TIL were present in 104 (15.8 %) of the 660 breast cancer cases. Their presence was associated with tumor size, grade, and lymph node status, and was differentially associated with the intrinsic subtypes of breast cancer. In univariate survival analyses, the presence of PD-1(+) TIL was associated with a significantly worse overall survival (HR = 2.736, p < 0.001). In subset analyses, the presence of PD-1(+) TIL was associated with significantly worse overall survival in the luminal B HER2(-) subtype (HR = 2.678, p < 0.001), the luminal B HER2(+) subtype (HR = 3.689, p < 0.001), and the basal-like subtype (HR = 3.140, p < 0.001). This is the first study to demonstrate that the presence of PD-1(+) TIL is associated with poor prognosis in human breast cancer, with important implications for the potential application of antibody therapies targeting the PD-1/PD-L1 signaling pathway in this disease.

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Figures

Fig. 1
Fig. 1
Representative photographs of PD-1+ TIL in a breast cancer tissue punch. a Tissue punch with PD-1+ TIL. Magnification 20× b PD-1+ TIL infiltrating a case of invasive ductal carcinoma. Magnification 400×
Fig. 2
Fig. 2
a Kaplan–Meier survival curve for overall survival depending on the presence of PD-1+ TIL (univariate analysis); b–f Kaplan–Meier survival curves for overall survival depending on the presence of PD-1+ TIL for the indicated breast cancer intrinsic subtypes
Fig. 3
Fig. 3
Representative flow cytometry data for PD-1 expression in human breast cancer. Consecutive gating on live cells/PD-1+ cells/CD3+ cells and subsequent gating on CD4+ and CD8+ cells in this subpopulation
See this image and copyright information in PMC

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